1. Field of the Invention
The present invention relates to the treatment of wounds, and particularly to a method of diagnosing and treating oxidative stress-impaired wound healing by testing for oxidative stress, and if present, administering effective amounts of antioxidants and/or Insulin-like Growth Factor 1 (IGF-1).
2. Description of the Related Art
Wound healing is a topic of considerable study. It involves a cycle of connective tissue matrix deposition, contraction, and epithelialization.
Several overlapping stages can be identified, and these are coordinated by a cascade of cell signaling proteins. Phases include clotting and inflammation, followed by new proliferation and differentiation of cells to fill the wound. The final phase begins by day 7 and includes remodeling of the new tissue, a process that can last for months. Under certain physiological conditions, however, wound healing is delayed, prolonged, or never reaches completion. Among the diseases that are associated with impaired wound healing are diabetes, hypercortisolemia, and chronic inflammation. Among diabetes patients alone, infected/ischemic foot ulcers are estimated to be the reason for about 25% of diabetes-related hospital visits, and precede 84% of lower extremity amputations among diabetes patients. The physiological stresses associated with such diseases as diabetes are believed to deregulate cell signaling and cytokine function at the site of the injury, resulting in improper cell behavior, including a prolonged inflammatory response and increased cell death. However, it has been thought that the final outcome of impaired wound healing can result from very different physiological processes. For example, TNF-α, which is known as a mediator of chronic inflammation, and cortisol (an anti-inflammatory agent that acts through a nuclear receptor) are transduced through different cell signaling pathways, but overabundance of either leads to chronic wounds. The inventors, however, have determined that a common mechanism shared by various types of delayed wound healing is an overabundance of reactive oxygen species (ROS). In diabetes, for example, the hyperglycemic state causes nutritional imbalance among cells at the site of the injury, and also causes oxidative stress. Normal tissue responds to ROS by expressing anti-oxidative stress proteins, such as glutathione, and enzymes that repair chemical damage caused by oxidation, but this response is impaired in the diabetic state.
The role of IGF-1 in diabetes and oxidative stress has been previously studied. IGF-1 is known to improve glucose disposal in humans. IGF-1 is also known to be a wound healing agent. In fact, the combination of IGF-1 and its binding proteins has been shown to accelerate wound healing in diabetic mice.
The role of antioxidants in treating the symptoms of diabetes has also been explored. For example, lipoic acid is known in the art to be useful for treating diabetes symptoms, such as retinopathy and neuropathy
IGF-1 shares partial sequence homology to insulin and is known to some degree to stimulate the same cellular receptors, and, as mentioned above, is also known to improve glucose handling in insulin-insensitive patients. However the biology of IGF-1 is incompletely understood. The tissue distribution of insulin action versus IGF-1 action is only partially overlapping. Although common intracellular signaling proteins are shared, the signaling outputs of insulin and IGF-1 differ in observable ways. For example, insulin may emphasize metabolic responses, while IGF-1 emphasizes mitogenic responses. It has been demonstrated that in particular situations and in particular tissues, insulin and IGF-1 action are not identical. Additionally insulin's role in wound repair has not been clearly delineated, whereas IGF-1 is critical.
Thus, a method of diagnosing and treating oxidative stress-impaired wound healing solving the aforementioned problems is desired.